ESR2 – Characterizing EV sub-population manufacture/secretion by prostate cancer cells, to identify vesicle subpopulation(s) that are functionally relevant for disease propagation and relevant as biomarkers

Host institution: Cardiff University, Cardiff, United Kingdom
Host department: Tissue Microenvironment Group, Division of Cancer & Genetics, School of Medicine
Supervisors: Prof. dr. Aled Clayton and Dr. Jason Webber

Project description
Cancer cells produce very small vesicles, which are released into the extracellular space. Such “extracellular vesicles” are highly complex in their molecular make-up, in their diversity of sizes and shapes, and potentially therefore exhibit different functional properties.

Our central hypothesis is that prostate cancer cells produce functionally distinct vesicle sub-populations, and by manipulating certain regulator proteins within the cells, the vesicle-populations can be altered; boosting or inhibiting particular vesicle sub-types. We postulate that by controlling vesicle production in this manner, we will be able to drastically impair cancer growth, angiogenesis, immunological evasion and eventual metastatic spread.

The study therefore will genetically manipulate prostate cancer cells, to target candidate vesicle regulating proteins. We aim to characterise in unprecedented detail the consequence of these manipulations on the biophysical diversity and also molecular content of vesicles being produced, and assign specific biogenetic pathways to particular vesicle types. Functional assays will be undertaken to better understand the relationships between vesicle sub-types and cancer-supporting functions, and a range of model systems are available for this.

The study will shed new light onto the complexities of vesicle production, and the endogenous mechanisms for their manufacture and secretion. The study will identify the vesicle subsets that are of greatest importance in terms of disease escalation, and provide novel options for their therapeutic manipulation. Molecular analysis of these “most dangerous” vesicles, will also provide a basis for a bio-specimen assay, and a means for identifying the presence of an aggressive disease signature in prostate cancer patients.

Type of contract
Fixed-term position for 36 months
Full-time, 37.5 hrs per week

Required expertise and skills in addition to the general eligibility criteria
The candidate should have experience in human cell culture, and common analytical techniques such as flow cytometry, fluorescence microscopy, protein analysis by ELISA, western blotting etc. Some experience/knowledge of molecular profiling methods in particular protein profiling will be an advantage.

We would very much value skills relating to genetic manipulation of cell lines, such as viral transductions delivering shRNA or CRISPR/Cas9 methods.

Enthusiastic and committed, the candidate should be a good communicator and be adaptable working as part of a team and also showing independence when needed. Willing to undertake all mandatory training, and adhere to University policies.

Websites
Prof. dr. Aled Clayton: https://www.cardiff.ac.uk/people/view/122903-clayton-aled

School of Medicine Post Grad Research: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/area/cancer-and-genetics

Contact details
For more information about this position, please contact:
Prof. dr. Aled Clayton: claytona@cardiff.ac.uk